Study Assessing the Safety and Efficacy of ABT-263 in Subjects With B-cell Chronic Lymphocytic Leukemia (CLL) Who Have Failed at Least One Prior Fludarabine-containing Regimen

This study has been withdrawn prior to enrollment.
(Sponsor has decided to not proceed with this study.)
Sponsor:
Collaborator:
Genentech
Information provided by:
Abbott
ClinicalTrials.gov Identifier:
NCT00918450
First received: May 22, 2009
Last updated: February 25, 2010
Last verified: February 2010
  Purpose

This is a Phase 2b, open-label, multicenter, global study assessing the safety and efficacy of ABT-263 in subjects with B-cell CLL who have failed at least one prior fludarabine-containing regimen.


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Drug: ABT-263
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2b Monotherapy Study of ABT-263 in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Assess the safety of ABT-263 by evaluating study drug exposure, adverse events, serious adverse events, all deaths, as well as changes in laboratory determinations and vital sign parameters. [ Time Frame: monthly (at a minimum) ] [ Designated as safety issue: Yes ]
  • Assess the objective response rate (partial response [PR] and confirmed complete response [CR]) of B-cell CLL subjects treated with ABT-263. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the effects of ABT-263 on duration of overall response, PFS and overall survival in subjects with B-cell CLL. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Assess the effects of ABT-263 on time to response, 12-month survival rate, time to disease progression (TTP), and disease control rate in subjects with B-cell CLL . [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Investigate the effects of ABT-263 on quality of life (FACT-Leu and EQ-5D), ECOG performance status, and biomarkers in subject with B-cell CLL. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: March 2010
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: ABT-263

Continuous dosing until disease progression using one of the following formulations:

25 mg/mL oral solution OR 50 mg/mL oral solution OR 2.0 grams/bottle powder for oral solution of 25 mg/mL when mixed OR 2.0 grams/bottle powder for oral solution of 50 mg/mL when mixed

Other Name: ABT-263

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >= 18 yrs of age, have B-cell CLL, failed at least 1 prior fludarabine-containing regimen.
  • Refractory to 1 fludarabine-containing regimen is defined as failure to achieve at least PR to the last fludarabine-containing regimen received, or disease progression while receiving the last fludarabine-containing regimen, or disease progression in responders (i.e., achieved a PR or CR) within 6 mos of the last cycle of the last fludarabine-containing regimen received (e.g., fludarabine monotherapy, FR, or FC) or in responders (i.e., achieved a PR or CR ) within 24 mos of the last cycle of FCR.
  • Intolerant to fludarabine is defined as discontinuation of therapy within 2 cycles due to side effects/toxicity from the last fludarabine-containing regimen.
  • ECOG score of <=1.
  • Adequate coagulation, renal, & hepatic function at Screening as follows:

    • Serum creatinine <= 2.0 mg/dL or calculated creatinine clearance >= 50 mL/min;
    • AST & ALT <= 3.0 x ULN;
    • Bilirubin <= 1.5 x ULN.
  • Gilbert's Syndrome may have a Bilirubin > 1.5 x ULN; aPTT, PT, not to exceed 1.2 x ULN.
  • Adequate bone marrow (BM) independent of any growth factor support (with the exception of subjects with BM heavily infiltrated with underlying disease [80% or more] who may use growth factor support to achieve adequate BM) at Screening as follows:

    • ANC >= 1000/µL;
    • Platelets >= 75,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening);
    • Hemoglobin >= 9.0 g/dL.
  • History of autologous BM transplant must be > 6 mos post transplant (prior to the 1st dose of study drug) & have adequate BM independent of any growth factor support (with the exception of subjects with BM that is heavily infiltrated with underlying disease [80% or more] who may use growth factor support to achieve adequate BM) at Screening as follows:

    • ANC >= 1500/µL;
    • Platelets >= 125,000/mm3;
    • Hemoglobin >= 10.0 g/dL.
  • Female subjects must be surgically sterile, postmenopausal (at least 1 year), or have negative results on a pregnancy test.
  • All female subjects not surgically sterile or postmenopausal (at least 1 year) & non-vasectomized male subjects must practice birth control.

Exclusion Criteria:

  • History/clinically suspicious for cancer-related CNS disease.
  • Undergone allogeneic stem cell transplant.
  • Undergone autologous stem cell transplant w/i 6 mos prior to 1st dose.
  • History/predisposing condition of bleeding or currently exhibits signs of bleeding.
  • Recent history of non-chemotherapy induced thrombocytopenic associated bleeding w/i 6 mos prior to 1st dose.
  • Active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
  • Active immune thrombocytopenic purpura or history of being refractory to platelet transfusions w/i 1 yr prior to 1st dose.
  • Currently receiving/requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications used to maintain the patency of a central IV catheter.
  • Significant history of cardiovascular disease, renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease.
  • Positive for HIV, Hepatitis B, or Hepatitis C.
  • Previous or current malignancies w/i the last 3 yrs:

    • except adequately treated in situ carcinoma of the cervix uteri;
    • basal or squamous cell carcinoma;
    • in situ carcinoma of the bladder;
    • or previous malignancy confined and surgically resected with curative intent.
  • Has Prolymphocytic leukemia or Richter's transformation to an aggressive B-cell malignancy.
  • Exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled systemic infection or diagnosis of fever and neutropenia w/i 1 week prior to study drug.
  • Prior exposure to ABT-263.
  • Received antibody therapy w/i 30 days prior to 1st dose.
  • Received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, or any investigational therapy w/i 14 days prior to the 1st dose, or has not recovered to <Gr2 clinically significant AE(s) /toxicity(s) of the previous therapy.
  • Received steroid therapy for anti-neoplastic intent, w/i 7 days prior to the 1st dose with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids.
  • Received aspirin w/i 7 days prior to the 1st dose.
  • Consumed grapefruit or grapefruit products w/i 3 days prior to 1st dose.
  • Females pregnant or breast-feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Sari Enschede, MD, Abbott Laboratories
ClinicalTrials.gov Identifier: NCT00918450     History of Changes
Other Study ID Numbers: M10-738
Study First Received: May 22, 2009
Last Updated: February 25, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 23, 2014